High-gravity technology intensified Knoevenagel condensation-Michael addition polymerization of poly (ethylene glycol)-poly (n-butyl cyanoacrylate) for blood-brain barrier delivery

查看全文 作　　者：Xingzheng [1]Liu;Chuanbo [1]Fu;Manting [1]Wang;Jiexin [1,2]Wang;Haikui [2]Zou;Yuan [1,2]Le;Jianfeng [1,2]Chen 机构地区：[1]State Key Laboratory of Organic-Inorganic Composites,Beijing University of Chemical Technology,Beijing 100029,China;[2]Research Centre of the Ministry of Education for High Gravity Engineering and Technology,Beijing University of Chemical Technology,Beijing 100029,China 出　　处：《Chinese Journal of Chemical Engineering》索引2022年第35卷第6期,共10页 基　　金：This work was supported by National Key Research and Development Program of China(2016YFA0201701). 摘　　要：Poly(ethylene glycol)-poly(n-butyl cyanoacrylate)(PEG-PBCA)is a remarkable drug delivery carrier for permeating blood-brain barrier.In this work,a novel high-gravity procedure was reported to intensify Knoevenagel condensation-Michael addition polymerization of PEG-PBCA.A series of PEG-PBCA containing different block ratios were synthesized with narrow molecular weight distribution of polydispersity indexes less than 1.1.Furthermore,the reaction time reduced 60%compared to conventional stirred tank reactor process.Chemical structures of as-prepared polymers were characterized.In vitro drug delivery performance was evaluated.The cytotoxicity of PEG-PBCA to brain microvessel endothelial cells(BMVEC)decreases with the extension of the PEG chain and the shortening of the PBCA chain.The polymer cellular uptake to BMVECs was better after improving hydrophilicity by PEG block.Results of bloodbrain barrier permeability demonstrated that medium length of PBCA chain and short PEG chain are favorable for hydrophobic Nile red permeation,while long PEG chain and short PBCA chain are beneficial to delivery water-soluble doxorubicin hydrochloride(Dox).The average apparent permeability coeffi-cient increased 1.7 and 0.25 times than that of raw Nile red and Dox,respectively.High-gravity intensi-fied condensation polymerization should have great potential in brain drug delivery system. 关 键 词：High-gravity technology Knoevenagel condensation-Michael addition polymerization Poly(ethylene glycol)-poly(n-butyl cyanoacrylate) Blood-brain barrier POLYMERIZATION Reactors